Oleanolic Acid Promotes Neuronal Differentiation and Histone Deacetylase 5 Phosphorylation in Rat Hippocampal Neurons
Hye-Ryeong Jo1,2,4, Sung Eun Wang1,4, Yong-Seok Kim1,3,4, Chang Ho Lee2,*, and Hyeon Son1,3,*
1Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763,
Korea, 2Department of Pharmacology, Hanyang University, Seoul 04763, Korea, 3Department of Biochemistry and Molecular
Biology, College of Medicine, Hanyang University, Seoul 04763, Korea, 4These authors contributed equally to this work.
*Correspondence: hyeonson@hanyang.ac.kr (HS); changholee57@gmail.com(CHL)
Received March 6, 2017; Revised May 10, 2017; Accepted May 12, 2017.; Published online June 30, 2017.
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Oleanolic acid (OA) has neurotrophic effects on neurons, although its use as a neurological drug requires further research. In the present study, we investigated the effects of OA and OA derivatives on the neuronal differentiation of rat hippocampal neural progenitor cells. In addition, we investigated whether the class II histone deacetylase (HDAC) 5 mediates the gene expression induced by OA. We found that OA and OA derivatives induced the formation of neurite spines and the expression of synapse-related molecules. OA and OA derivatives stimulated HDAC5 phosphorylation, and concurrently the nuclear export of HDCA5 and the expression of HDAC5 target genes, indicating that OA and OA derivatives induce neural differentiation and synapse formation via a pathway that involves HDAC5 phosphorylation.
Keywords: HDAC5, neuronal differentiation, oleanolic acid

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30 June 2017 Volume 40,
Number 6, pp. 379~439

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